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endemic fungal pneumonia





fungal pneumonia associated with immunosuppression




What are some of the major characteristics of endemic mycoses?

thermally dimorphic fungi that exist in nature, soil

hyphal form in the environment, yeast form in tissue

inhalation leads to pulmonary infection and dissemination

no evidence of transmission among humans or animals

otherwise healthy individuals are infected


general characteristics of Histoplasma capsulatum

soil-based fungus associated with river valleyes and bird and bat guano

in the US, mostly endemic to Ohio and Mississippi river valleys

acquisition associated with disruption of the soil by excavation or construction, inhilation and pulmonary infection

dimorphic - mycelial (37 degrees C or higher) and yeast phase

hallmark of tissure response is caseating or noncaseating granulomas


clinical manifestations of H. capsulatum

> 90% go unrecognized, asymptomatic or mild influenza-like illness

Ghon complex and pulmonary calcifications are common in healed pulmonary histoplasmosis


complications of H. capsulatum infection

mediastinal lymphadenitis

mediastinal fibrosis

cavitary pulmonary histoplasmosis

progressive disseminated histoplasmosis (PDH)


diagnosis of Histoplasmosis

culture in brain heart infusion agar with blood, antibiotics, and cyclohexamide

cultures incubated for 30 degrees C for up to 6 weeks

majority cultures show grwoth within 7 days

sputum culture


rapid diagnosis by polysaccharide antigen detection in urin, serum, BAL fluid


histopathology of Histoplasmosis

yeast visualized poorly by H and E stain

better seen with periodic acid-Schiff (PAS) and Gomorimethenamine silver (GMS) stains


treatnebt if Histoplasmosis

acute pulmonary disease

if symptoms less than 4 weeks no treatment

if symptoms greater than 4 weeks itraconazole for 6-12 weeks

chronic pulmonary disease, disseminated disease, granulomatous mediastinitis - Amphotericin B then Itraconazole for 6-24 months


general characteristics of Blastomyces dermatitidis

organism found in warm, moist soil of wooded areas rich in organic debris, such as decaying vegetation

dimorphic funcgus, mycelial form at room temeprature and yeast form at 37 degrees C

endemic to North America, including southeasterna nd south central states, especially those bordering the Mississippi and Ohio River basins and the Great Lakes

usualt portal of entry in humans is through the inhalation of conidia, which convert to the yeast phase in the lung

the typical inflammatory response consists of clusters of neutrophils and noncaseating granulomas with epithelioid and giant cells

Broad Based Budding yeast


clinical manifestation of Blastomycosis

pulmonary blastomycosis - acute or chronic, mimics infection with pyogenic bacteria, TB, other fungal infections, and malignancy

extrapulmonary manifestations - cutaneous disease and bone infection


diagnosis of Blastomycosis

definitive diagnosis requires recovery in culture

can also examine secretions

histopathological examination - pyogranuloma, GMS stain

antigen assay

serologic testing - complement fixation, immunodiffusion, radioimmunoassay, ezyme immunoassay


treatment of Blastomycosis

asymptomatic disease limited to the lungs - follow the patient closely for disease progression or dissemination

in immunocompromized, progressive pulmonary disease, or extrapulmonary disease - amphotericin B and itraconazole


What are the two species of Coccidioides?

Coccidioides immitis (CA)

Coccidioides Posadasii (other states and countries outside the US)


Where is Coccidioidomycosis endemic to?

southwestern US, especially in New Mexico, Arizona, and the San Joaquin Valley of California


general characteristics of Coccidioides spp.

dimorphic fungi that exists as either a mycelium or a spherule

found in the soil, grows by apical extension, true septa form along course

alternating mycelial cells undergo autolysis

remaining cells (arthroconidida) develop a hydrophobic outer layer and can remain viable for long periods

fragile attachments of arthroconidia to adjacent cell remnants make them prone to separation by physical disruption or mild air turbulence

arthroconidia become airborne and can be inhaled and deposited in the lungs


Coccidioides spp. development in the lungs

arthroconidia remodel into spherical cells, shedding outer wall

cell multiplication -> spherule divide into endospores

in tissue, spherules can develop to a size of 75 microns in diameter, containing 100 endospores

spherule matures, outer wall thins and ruptures

endospores are released to propagate in tissue or revert to mycelial growth if removed from tissue


clinical manifestations of Coccidioidomycosis

asymptomatic or subclinical

non-specific respiratory infection

pulmonary nodule - hard to distinguish form malignancy

chronic fibrotic pneumonia

disseminated disease - skin, bone and joints, meningitis (fatal if untreated)


diagnosis of Coccidioidomycosis

not detected by Gram staining

spherules visualized in tissue by H and E stains, silver or periodic acid-Schiff stains

grow well on most media after 5-7 days of incubation - highly infectious cultures

serologic testing - most frequent means of diagnosing primary infection, highly specific for active infection

urine antigen testing


treatment of Coccidioidomycosis

vast majority of early infections resolve without specific antifungal therapy

solitary pulmonary nodule - no treatment

cavitary disease - no treatment if asymptomatic

severe pneumonia and chronic progressive fibrocavitary pulmonary or disseminated disease - treat with amphotericin B, fluconazole, or itraconazole for 3-6 months

diffuse pneumonia needs one year or more of treatment

meningitis or ongoing immunosuppression is life-long


general characteristics of Aspergillus spp.

ubiquitous, found in soil, water, food, air, decaying vegetation

normal pulmonary host defenses - rarely develop disease

prolonged and profound neutropenia result in high risk for invasive aspergillosis

usually infect through inhaled conidia

infection progresses across tissue planes invades blood vessels leading to infarction of distal tissue


clinical manifestations of Aspergillosis

fever, chest pain, shortness of breath, cough, and/or hemoptysis

patients with severe neutropenia frequently present with fever and no localizing pulmonary symptoms


diagnosis of Aspergillosis

chest CT more sensitive than x-ray for detecting earliest stages of disease

- single or multiple nodules with or without caviation

- patchy consolidation or peribronchial infiltrates

"Halo sign"

infection may involve sinuses, CNS, heart, and skin

histopathology - septate hyphae with acute angle branching

antigen assays in serum or BAL - galactomannan and beta-d-glucan


Halo sign

in CXR for aspergillosis, nodule with surrounding ground glass infiltrate - hemorrhage into area surrounding fungal infection


treatment of Aspergillosis

voriconazole is the treatment of choice

alternatives include amphotericin B, the echinocandins, posaconazole, and itraconazole

recovery of neutrophils in patients with neutropenia is critical to recovery


general characteristics of Pneumocystic jiroveci

fungus, morphologic forms include cysts, sporozites, and trophozoites

worldwide distribution - mostly healthy children exposed by 3-4

airborne and person-to-person transmission

disease associated with defects in cellular and humoral immunity

Pneumocystis does not appear unless CD4 count is less than 200


clinical presentation of Pneumocystis

progressive exertional dyspnea, fever, non-productive cough, chest discomfort, worsens over days-weeks


diagnosis of Pneumocystis

laboratory findings include hypoxemia and elevated LDH

CXR findings include diffuse bilateral symmetrical intersittial infiltrates

chest CT shows patchy ground glass attenuation

diagnosis confirmed by identification of the organism by immunofluorescent antibody staining of induced sputum or BAL fluid with excellent sensitivity and specificity


treatment of Pneumocystis

trimethoprim-sulfamethoxazole or trimethroprim plus dapsone, clindamycin plus primaquine, atovaquone, and pentamidine

corticosteroids for severe disease, decreases inflammation with dying organisms